Brain function and behaviour related to development and training of working memory

Sammanfattning: Training of working memory (WM) is a research field that could result in new therapeutic breakthroughs for people with impaired WM functions. In support of this view, research in our group has previously shown that WM training could increase WM capacity in children with attention deficits and in healthy adults. Apart from that study, there had been no previous literature on WM training presenting clear evidence for a clinically relevant change on WM capacity or brain activity following WM training. Study II and III were designed to investigate these issues. Only a few previous studies have investigated the development of brain activity related to WM. The results from those previous studies indicate that the development of WM is related to changes in activity in the frontal and parietal cortex. The aim of the developmental studies in this thesis (Study I and IV) was to extend those previous findings using two new approaches: 1) integration of data on brain function and brain structure and 2) investigation of a critical WM function i.e. the ability to ignore distraction. Previous research in our group showed that increased brain activity in prefrontal and parietal areas underlie the development of WM. In Study I, we sought to investigate how this development is related to the development of brain connectivity. Our aim was to present a network of brain structure and function underlying development of WM, which has previously never been shown. Consistently, the results from Study I showed that development of WM was related to a frontoparietal network of brain regions where brain activity and connectivity showed a similar developmental trend. The published research on brain activity related to training of WM is very scarce. Therefore, Study II aimed at investigating the long-term effects of WM training on brain activity using a training paradigm that was designed to optimise the training effects for each individual. For the first time we were able to show that training of a cognitive function, WM, could result in changes in brain activity in the adult human brain in task-related areas. In Study III the aim was to establish whether WM training could result in clinically relevant effects on performance and behaviour such that it could be used as a new therapy for groups of people with attention deficits. The resulting analyses included data from 44 children, diagnosed with ADHD, who had participated in a five week WM training program. Performance on executive functions, including WM, and behavioural ratings of ADHD symptoms, improved significantly as an effect of WM training. In Study IV we investigated the development of brain activity related to the ability to ignore distraction. This ability is central to WM since distracting stimuli must be ignored in order to keep information in WM. There is no previous published research on the neural mechanisms underlying the development of this important ability. The unravelling of those mechanisms would add to the understanding of the neurobiology related to disorders affecting attention and impulsivity, in addition to increasing our knowledge about WM functions. Furthermore, Study IV was designed to analyse developmental changes in brain activity related to each phase of a WM task. Importantly, we found that development of WM was related to increased brain activity in frontal and parietal areas during maintenance of information in WM. The ability to ignore distraction was related to brain activity in the prefrontal cortex in adults. In children another part of the prefrontal cortex was related to the presence of distraction and this area corresponded to the area where information was maintained. To conclude, this thesis demonstrates previously unknown data on the capacity of the human brain in relation to the healthy and deficient WM system and identifies brain areas that are crucial for the development of this system.